Abnormal body and vocal fold hydration has been assumed to cause, maintain or exacerbate voice disorders. Voice disorders associated with abnormal laryngeal or vocal fold water transport are prevalent and include edema, secretory disorders, benign lesions, pre cancerous and cancerous lesions, scarring and drying from drugs, dehydrated air, radiation, thermal or chemical burns. A rationale for future treatments demands that we understand how to regulate the mechanisms that control vocal fold water transport. The research plan aims to test the overall hypothesis that the ease of phonation can be regulated by selectively increasing or decreasing vocal fold hydration, epithelial cell volume and transepithelial water transport. The hypothesis is based on our novel observations about mechanisms of epithelial water/ion transport in the vocal folds. Kimberly Fisher, Ph.D. is a Speech Language Pathologist and tenure-track, Assistant Professor at Northwestern University, Department of Communication Disorders. Her goal is to establish a new line of basic and applied research into mechanisms that control vocal fold water transport and their role in the regulation of voice. She plans to investigate the phonatory consequences of manipulating water and ion transport in the vocal folds of humans and dogs. She will regulate the water and ion transport across native, canine vocal fold tissue by selectively inhibiting epithelial ion channels a transporters. The strength of the approach lies in the systematic integration of human, canine in vivo, and in vitro models. The studies may lead to new non-invasive, pharmacologic treatments for airway, laryngeal and voice disorders. The career development plan exploits the substantial research resources across Northwestern's Departments of Communication Sciences and Disorders, Otorhinolaryngology, Radiology and Nephrology, as well as the Pulmonary Biophysics and Bioengineering Research Laboratory at University of Illinois at Chicago. Donovan Yeates, Ph.D., a federally-funded scientist in the area of physiological regulation of ion and water transport in tracheal epithelium, will serve as the candidate's primary mentor for this K08 application. Charles Larson, Ph.D., also with current NIH funding, will provide mentorship regarding electrically evoked phonation in animal models. The mentors will be directly involved with the experiments and in the training of the candidate. The plan further includes regular consultations with other experienced voice researchers involved in Northwestern Center Grant, and The National Center for Voice and Speech. The academic plan involves coursework in cellular/molecular biology, the physiology of water and ion transport, laryngeal and airway autonomics, advanced statistics and research ethics. A primary goal is the development of an R01 proposal by the candidate during years 3-4 of this project.